chr3-43690745-C-T

Variant names:

• chr3-43690745-C-T
• rs79436573
• ENST00000428831.1:c.-236G>A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001346468.2(ANO10):​c.-12+772G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0238 in 426,546 control chromosomes in the GnomAD database, including 174 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.021 (55 hom., cov: 33)
  • Exomes 𝑓: 0.025 (119 hom.)
• Consequence: ANO10 NM_001346468.2 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.57

Genes affected

ANO10 (HGNC:25519): (anoctamin 10) The transmembrane protein encoded by this gene belongs to the anoctamin family of calcium-activated chloride channels, also known as the transmembrane 16 family. The encoded protein contains eight transmembrane domains with cytosolic N- and C-termini. Defects in this gene may cause autosomal recessive spinocerebellar ataxia-10. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2016]

ABHD5 (HGNC:21396): (abhydrolase domain containing 5, lysophosphatidic acid acyltransferase) The protein encoded by this gene belongs to a large family of proteins defined by an alpha/beta hydrolase fold, and contains three sequence motifs that correspond to a catalytic triad found in the esterase/lipase/thioesterase subfamily. It differs from other members of this subfamily in that its putative catalytic triad contains an asparagine instead of the serine residue. Mutations in this gene have been associated with Chanarin-Dorfman syndrome, a triglyceride storage disease with impaired long-chain fatty acid oxidation. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 3-43690745-C-T is Benign according to our data. Variant chr3-43690745-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 670436.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0847 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ABHD5	NM_016006.6	c.-248C>T		upstream_gene_variant		ENST00000644371.2	NP_057090.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ABHD5	ENST00000644371.2	c.-248C>T		upstream_gene_variant			NM_016006.6	ENSP00000495778.1

Frequencies

GnomAD3 genomes AF: 0.0211 AC: 3207 AN: 152198 Hom.: 55 Cov.: 33

Gnomad AFR AF: 0.00781

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0232

Gnomad ASJ AF: 0.0268

Gnomad EAS AF: 0.0273

Gnomad SAS AF: 0.0916

Gnomad FIN AF: 0.00499

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0255

Gnomad OTH AF: 0.0249

GnomAD4 exome AF: 0.0253 AC: 6932 AN: 274230 Hom.: 119 Cov.: 2 AF XY: 0.0266 AC XY: 3770 AN XY: 141602

Gnomad4 AFR exome AF: 0.00724

Gnomad4 AMR exome AF: 0.0384

Gnomad4 ASJ exome AF: 0.0324

Gnomad4 EAS exome AF: 0.0326

Gnomad4 SAS exome AF: 0.0658

Gnomad4 FIN exome AF: 0.00729

Gnomad4 NFE exome AF: 0.0237

Gnomad4 OTH exome AF: 0.0245

GnomAD4 genome AF: 0.0211 AC: 3212 AN: 152316 Hom.: 55 Cov.: 33 AF XY: 0.0214 AC XY: 1594 AN XY: 74472

Gnomad4 AFR AF: 0.00796

Gnomad4 AMR AF: 0.0232

Gnomad4 ASJ AF: 0.0268

Gnomad4 EAS AF: 0.0270

Gnomad4 SAS AF: 0.0917

Gnomad4 FIN AF: 0.00499

Gnomad4 NFE AF: 0.0255

Gnomad4 OTH AF: 0.0246

Alfa AF: 0.0209 Hom.: 7

Bravo AF: 0.0202

Asia WGS AF: 0.0450 AC: 157 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 18, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.12
DANN	Benign	0.88

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs79436573; hg19: chr3-43732237;